RESUMO
Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3-60.0%) sensitivity and a 98.5% (95% CI: 97.0-99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4-90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3-68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs.
Assuntos
Hemangiossarcoma , Osteossarcoma , Animais , Biomarcadores Tumorais/genética , Cães , Detecção Precoce de Câncer , Testes Hematológicos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Biópsia LíquidaRESUMO
Rhinoscopy was performed on 10 dogs with sinonasal aspergillosis (SNA). Direct access to the sinus via the nasal ostium was possible with a flexible endoscope to allow sinuscopy. Debridement of fungal plaques in the frontal sinus and the nasal cavity was performed, and a sinus and nasal deposition therapy with clotrimazole (1%) cream was made under rhinoscopic guidance. No oral medication was administered following the procedure. A rhinoscopic follow-up was performed monthly until cure. Six of ten (60%) dogs presented fungal plaques in the nasal cavity and in the frontal sinus and 4/10 (40%) dogs presented fungal plaques only in the frontal sinus. Five of ten (50%) dogs were considered to be cured at the first follow-up rhinoscopy, 4/10 (40%) after the second follow-up, and 1/10 (10%) after the third. Two dogs had delayed recurrence of SNA rhinoscopically assessed 12 and 21 mo, respectively, after the last clotrimazole treatment. Endoscopic debridement of fungal plaques and clotrimazole (1%) cream deposition therapy seems to be a valuable minimally invasive technique for SNA treatment in dogs without the use of complementary oral medication. Delayed recurrence is a potential finding following treatment of SNA.